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Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior

Nature Genetics volume 31, pages 363–369 (2002)Cite this article

Abstract

Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing.

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Figure 1: Generation of Ucn mutant mice.
Figure 2: Ucn mutant mice show normal hormonal response to restraint stress and normal feeding response to 24-h food deprivation.
Figure 3: Increased anxiety-like behavior of Ucn-null mice in elevated plus maze and open-field tests.
Figure 4: Decreased Crhr2 mRNA expression in the brains of Ucn mutant mice.
Figure 5: Extensive network of Ucn-immunoreactive terminals and expression of CRH receptors in the inner hair-cell region of the mouse organ of Corti.
Figure 6: Impairment of hearing in Ucn mutant mice.

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Acknowledgements

We thank P. Sawchenko for bringing to our attention the potential role of Ucn on the auditory system. We also thank P. Chen for help with the image analysis, K. Creehan for animal assistance and S. Guerra and M. Arends for editorial assistance. This work was supported in part by grants from the US National Institutes of Health (to S.F.H., M.C.L., W.V. and K.F.L.), the Robert J. and Helen C. Kleberg Foundation, the Ludwick Family Foundation and the Foundation for Research. C.L. and L.Z. were supported by NIH National Research Service Award fellowships. This is publication number 14789-NP from The Scripps Research Institute. K.-F.L. is a Pew Scholar.

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Author notes

  1. Douglas E. Vetter

    Present address: Tufts University School of Medicine, Department of Neuroscience, Boston, Massachusetts, USA

  2. George W. Smith

    Present address: Department of Animal Science, Michigan State University, East Lansing, Michigan, USA

  3. Douglas E. Vetter, Chien Li and Lingyun Zhao: These authors contributed equally to this work.

Authors and Affiliations

  1. The Salk Institute for Biological Studies, La Jolla, 92037, California, USA

    Douglas E. Vetter, Chien Li, Lingyun Zhao, George W. Smith, Yelena Marchuk, Stephen F. Heinemann, Wylie Vale & Kuo-Fen Lee

  2. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA

    Angelo Contarino & George F. Koob

  3. Massachusetts Eye and Ear Infirmary and Department of Otology and Laryngology, Eaton Peabody Lab, Harvard Medical School, Boston, Massachusetts, USA

    M. Charles Liberman

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Vetter, D., Li, C., Zhao, L. et al. Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior. Nat Genet 31, 363–369 (2002). https://doi.org/10.1038/ng914

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